KR860003514A - How contrast and chemotherapeutic agents deliver encapsulated micelles to human tumors - Google Patents

How contrast and chemotherapeutic agents deliver encapsulated micelles to human tumors Download PDF

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KR860003514A
KR860003514A KR1019850007773A KR850007773A KR860003514A KR 860003514 A KR860003514 A KR 860003514A KR 1019850007773 A KR1019850007773 A KR 1019850007773A KR 850007773 A KR850007773 A KR 850007773A KR 860003514 A KR860003514 A KR 860003514A
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tumor
particles
chemotherapeutic agent
phospholipid
micelles
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KR900004802B1 (en
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아네트 프레잔트(외 4) 캐리
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원본 미기재
시티 오브 호프 네쇼날 메디칼 센터(외1)
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Priority claimed from US06/663,550 external-priority patent/US5441745A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1217—Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
    • A61K51/1234—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
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  • Physics & Mathematics (AREA)
  • Dispersion Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Micellular particle compositions for delivering intact micellular particles containing imaging agents or chemotherapeutic agents to tumors within a body for the diagnosis and treatment of such tumors. The micellular particles are small, less than 2000 ANGSTROM and incorporate pure, neutral phospholipid molecules preferably containing at least 18 carbon atoms, in their external surface. Enhanced delivery of the micellular particles containing imaging agents or chemotherapeutic agents may be achieved by introducing an initial group of micellular particles containing positively charged molecules extending externally from the particles to block phagocytic cells present in tissues of the body.

Description

조영제 및 화학요법제가 캡슐화된 미셀입자를 인체의 종양에 전달시키는 방법How contrast and chemotherapeutic agents deliver encapsulated micelles to human tumors

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음As this is a public information case, the full text was not included.

제1도는 형액중의 방사성표지를 한 인지질 소포의 정화치(精化値) 및 종양중의 축적의 시간경과를 나타낸 도표임.FIG. 1 is a chart showing the purification of phospholipid vesicles labeled with radiolabels and the time course of accumulation in tumors.

제2도은 감마선 섭동각(角) 상관(PAC) 분광법에 의해 측정된 혈액 및 종양중에 잔존하는 방사성 표지를 한 손상되지 않은 인지질 소포의 백분율을 나타낸 그래프임.FIG. 2 is a graph showing the percentage of intact phospholipid vesicles with radiolabel remaining in the blood and tumors as measured by gamma ray perturbation angle correlation (PAC) spectroscopy.

Claims (22)

a. 화학적으로 순수한 인지질 분자로 되는 2000Å 미만의 중성소형 미셀입자를 제공하고, b. 종양중의 상기 입자의 위치를 검측하기 위해서 조영제를 상기 미셀입자 또는 종양치료용 화학요법제와 결합시키고, c. 상기 단계 b의 미셀입자를 인체의 혈류내로 주입시켜서 종양내에서 상기 입자들은 손상되지 아니한채로 재치시킴을 특징으로 하는 전단 또는 치료용 시약으로 인체중 종양을 표적시키는 방법.a. Providing less than 2000 micron small micron micelles of chemically pure phospholipid molecules, b. Combining a contrast agent with the micelle or tumor therapy chemotherapeutic agent to detect the location of the particles in the tumor, c. Injecting the micelle particles of the step b into the bloodstream of the human body to place the particles in the tumor intact in the tumor, characterized in that to target the tumor in the human body with shear or therapeutic reagents. 제1항에 있어서, 상기 화학적으로 순수한 인지질 분자가 탄소원자수가 적어도 18개인 탄화수소 사슬을 함유하는 방법.The method of claim 1, wherein the chemically pure phospholipid molecule contains a hydrocarbon chain having at least 18 carbon atoms. 제1 또는 2항에 있어서, 상기 인지질이 디스테아로일 포스파틸콜린인 방법.3. The method of claim 1 or 2, wherein said phospholipid is distearoyl phosphatylcholine. 제1 또는 2항에 있어서, 상기 화학요법제가 메토트렉세이트인 방법.The method of claim 1, wherein the chemotherapeutic agent is methotrexate. 제1 또는 2항에 있어서, 상기 조영제가 방사성원소, 특히 감마방사체로서, 특히 인듐-111인 방법.Method according to claim 1 or 2, wherein the contrast agent is a radioactive element, in particular a gamma emitter, in particular indium-111. 제4항에 있어서, 상기 인듐-111를 약한 킬레이터, 특히 니트릴토트리아세트산으로 킬레이트시켜서 상기 방사성 표지체와 강한 결합을 이루는 특정위치에서 약한 킬레이터를 다른 물질로 대치시키는 방법.5. A method according to claim 4, wherein the indium-111 is chelated with a weak chelator, in particular nitrile totriacetic acid, to replace the weak chelator with a different material at a specific position that forms a strong bond with the radiolabel. 제1항에 있어서, 상기 중성 미셀입자가 또한 인지질중량에 기초하여 0∼50중량%의 콜레스테롤과 결합하는 방법.The method of claim 1 wherein said neutral micelles also bind 0-50% by weight of cholesterol based on phospholipid weight. a. 양으로 하전된 물질과 함께 결합된 입자로부터 외부로 신장되는 양하전 분자를 갖는 화학적으로 순수한 인지질 분자로 되는 소형 미셀입자의 제1군을 제공하고, b. 상기 양으로 하전된 입자의 제1군을 인체의 혈류내로 주입시켜서 인체중 식세포를 차단시키고, c. 상기 종양의 위치를 측정하기 위한 조영제 또는 종양을 치료하기 위한 화학요법제를 결합시킨, 화학적으로 순수한 인지질분자로 되는 2000Å 미만의 중성 소형 미셀입자의 제2군을 제공하고, d. 상기 식세포를 차단시킨 다음에, 상기 조영제 또는 화학요법제를 갖는 중성 미셀입자의 제2군을 인체의 혈류에 주입시켜서, 종양내에서 손상되지 않은 상기 입자 및 화학요법제를 재치시킴을 특징으로 하는 상기 종양의 진단 또는 치료용 조영제 또는 화학요법제를 함유하는 손상되지 않은 미셀입자를 종양내에 재치시키는 방법.a. Providing a first group of small micelles of chemically pure phospholipid molecules having positively charged molecules extending outwardly from particles bound together with the positively charged material, b. Injecting a first group of positively charged particles into the bloodstream of the human body to block phagocytes in the human body, c. Providing a second group of less than 2000 micron neutral small micelles of chemically pure phospholipid molecules incorporating a contrast agent to measure the location of the tumor or a chemotherapeutic agent to treat the tumor, d. After blocking the phagocytes, a second group of neutral micelles containing the contrast agent or chemotherapeutic agent is injected into the bloodstream of the human body to reload the intact particles and chemotherapeutic agent. And intact micelles containing the contrast or chemotherapeutic agent for diagnosis or treatment of the tumor. 제8항에 있어서, 화학적으로 순수한 인지질분자의 상기 제2군이 탄소원자수가 적어도 18개인 탄화수소를 함유하는 방법.The method of claim 8, wherein said second group of chemically pure phospholipid molecules contains a hydrocarbon having at least 18 carbon atoms. 제8항에 있어서, 상기 중성 미셀입자가 또한 인지질 중량에 기초하여 0∼50중량%의 콜레스테롤과 결합하는 방법.The method of claim 8, wherein said neutral micelles also bind 0-50% by weight of cholesterol based on the weight of phospholipids. 제8항에 있어서, 인지질분자로부터 외부로 신장되는 상기 양하전 분자가 아미노기를 함유하는 지질 용해성 분자인 방법.The method of claim 8, wherein the positively charged molecule that extends outward from the phospholipid molecule is a lipid soluble molecule containing an amino group. 제12항에 있어서, 상기 양으로 하전된 분자가 지질 용해성 분자의 아미노-사카라이드 유도체인 방법.The method of claim 12, wherein said positively charged molecule is an amino-saccharide derivative of a lipid soluble molecule. 제12항에 있어서, 상기 양으로 하전된 분자가 콜법스테롤의 아미노-사카라이드 유도체인 방법.13. The method of claim 12, wherein said positively charged molecule is an amino-saccharide derivative of cholesterol. 제13항에 있어서, 아미노-사카라이드 유도체가 콜레스테롤의 아미노만노오스 또는 아미노만니톨 유도체인 방법.The method of claim 13, wherein the amino-saccharide derivative is an aminomannose or aminomannitol derivative of cholesterol. 제8항에 있어서, 상기 인지질이 디스테아로일 포스파티딜콜린인 방법.The method of claim 8, wherein said phospholipid is distearoyl phosphatidylcholine. 제8항에 있어서, 상기 화학요법제가 메토트렉세이트인 방법.The method of claim 8, wherein the chemotherapeutic agent is methotrexate. 제8항에 있어서, 상기 조영제가 니트릴로트리아세트산에 킬레이트된 인듐-111인 방법.The method of claim 8, wherein the contrast agent is indium-111 chelated to nitrilotriacetic acid. 제1 또는 8항에 있어서, 상기 소형 미셀입자가 구형 단층상 인지질 소포의 형태인 방법.9. The method of claim 1 or 8, wherein the small micelle particles are in the form of spherical tomographic phospholipid vesicles. 화학적으로 순수한 인지질분자로 되고, 종양의 치료 또는 진단용 조영제 또는 화학요법제를 결합시킨 2000Å 미만의 미셀입자를 함유하는 종양.Tumors that are chemically pure phospholipid molecules and contain micelle particles of less than 2000 microns incorporating a therapeutic or diagnostic contrast agent or chemotherapeutic agent. 제19항에 있어서, 상기 조영제가 인듐-111인 종양.20. The tumor of claim 19, wherein the contrast agent is indium-111. 제19항에 있어서, 상기 화학요법제가 매토트렉세이트인 종양.20. The tumor of claim 19, wherein said chemotherapeutic agent is methotrexate. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임※ Note: The disclosure is based on the initial application.
KR1019850007773A 1984-10-22 1985-10-22 Micellular particles encapsulating imaging and chemotherapeutic agents to turmos in a body KR900004802B1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US06/663,503 US5435989A (en) 1982-03-30 1984-10-22 Method of targeting a specific location in a body
US663550,663503 1984-10-22
US663,503 1984-10-22
US663,550 1984-10-22
US06/663,550 US5441745A (en) 1982-03-30 1984-10-22 Method of delivering micellular particles encapsulating chemotherapeutic agents to tumors in a body

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KR860003514A true KR860003514A (en) 1986-05-26
KR900004802B1 KR900004802B1 (en) 1990-07-06

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JP (1) JPH0747533B2 (en)
KR (1) KR900004802B1 (en)
AT (1) ATE64298T1 (en)
CA (1) CA1298548C (en)
DE (2) DE19675031I2 (en)
DK (2) DK482685D0 (en)
HK (1) HK119993A (en)
IE (1) IE58659B1 (en)
LU (1) LU88811I2 (en)
NL (1) NL960020I1 (en)

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IE60901B1 (en) * 1986-08-21 1994-08-24 Vestar Inc Improved treatment of systemic fungal infections with phospholipid particles encapsulating polyene antifungal antibiotics
US5043107A (en) * 1986-08-21 1991-08-27 Vestar Research, Inc. Preparation small unilamellar vesicles including polyene antifungal antibiotics
IL88076A (en) * 1987-10-28 1993-01-14 Nippon Shinyaku Co Ltd Fat emulsions as drug carriers
AU598958B2 (en) 1987-11-12 1990-07-05 Vestar, Inc. Improved amphotericin b liposome preparation
US5648532A (en) * 1993-06-03 1997-07-15 The Regents Of The University Of California Compositions for boron neutron capture therapy and methods thereof
JPH10513466A (en) * 1995-02-09 1998-12-22 シェリング アクチェンゲゼルシャフト Liposomes containing contrast agents for visualizing intravascular space
NO312708B1 (en) * 2000-02-21 2002-06-24 Anticancer Therapeutic Inv Sa Radioactive liposomes for therapy
WO2005048987A1 (en) * 2003-11-21 2005-06-02 Fuji Photo Film Co., Ltd. Contrast medium comprising liposomes containing hydrophobic chelate compound
EP1745788A1 (en) * 2005-07-22 2007-01-24 KTB Tumorforschungsgesellschaft mbH Acyglycerophospholipids for treating cancer and cachexia
EP2668961A4 (en) * 2010-11-19 2016-07-06 Univ Sapporo Medical Combined pharmaceutical preparation

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US4310505A (en) * 1979-11-08 1982-01-12 California Institute Of Technology Lipid vesicles bearing carbohydrate surfaces as lymphatic directed vehicles for therapeutic and diagnostic substances
JPS59122423A (en) * 1982-12-28 1984-07-14 Green Cross Corp:The Carcinostatic-containing fatty emulsion
JPS59163315A (en) * 1983-03-09 1984-09-14 Mitsui Pharmaceut Inc Carmofur-containing liposome

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DE19675031I2 (en) 2008-04-10
HK119993A (en) 1993-11-12
IE58659B1 (en) 1993-11-03
NL960020I1 (en) 1996-11-01
DK484585D0 (en) 1985-10-22
JPH0747533B2 (en) 1995-05-24
EP0179444A3 (en) 1987-08-12
DK167556B1 (en) 1993-11-22
CA1298548C (en) 1992-04-07
EP0179444B1 (en) 1991-06-12
EP0179444A2 (en) 1986-04-30
DK484585A (en) 1986-04-23
IE852602L (en) 1986-04-22
DE3583204D1 (en) 1991-07-18
ATE64298T1 (en) 1991-06-15
DK482685D0 (en) 1985-10-21
LU88811I2 (en) 1996-11-05
KR900004802B1 (en) 1990-07-06
JPS61158932A (en) 1986-07-18

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